It is the purpose of this research to study the topology (asymmetry, near-neighbors) of phospholipids and proteins in cell membranes and to elucidate the mechanism of action of hormones at the membrane level. The plasma membrane from eukaryote cells, (rat heart, human and avian erythrocytes, human adipocytes and rat adipocytes) and prokaryote cells will serve as the source for these membranes. The arrangement of phospholipids and proteins in the membrane will be examined by use of penetrating and non-penetrating chemical probes and cross-linking agents. The nature of hormone binding (insulin and catecholamines) to the membranes will be studied and attempts will be made to see if and how the hormone binding is altered in abnormal states such as diabetes and obesity, hypothyroidism and hyperthryoidism. It is hoped to elucidate the biochemical mechanism whereby thyroxine regulates the catecholamine response in cardiac ventricle cells. The mechanism coupling of the hormone receptor with adenylate cyclase activation or inhibition will be studied by correlating hormone binding with adenylate cyclase activity and by use of hormone structural analogs. Attempts to isolate and purify the catecholamine receptor in the membrane by use of photochemical coupling techniques. For this study attempts will be made to synthesize a radioactive photoactive antagonist. This work will be done with the catecholamine receptor in turkey erythrocyte membranes.